ABSTRACT
Cyclic voltammetry (CV) and electron spin resonance (ESR) techniques were used in the investigation of novel palladium complexes with bioactive thiosemicarbazones derived from 5-nitrofurane or 5-nitrofurylacroleine. Sixteen palladium complexes grouped in two series of the formula [PdCl(2)HL] or [PdL(2)] were studied. ESR spectra of the free radicals obtained by electrolytic reduction were characterized and analyzed. The ESR spectra showed two different hyperfine patterns. The stoichiometry of the complexes does not seem to affect significantly the hyperfine constants however we observed great differences between 5-nitrofurane and 5-nitrofurylacroleine derivatives. The scavenger properties of this family of compounds were lower than Trolox.
Subject(s)
Palladium/chemistry , Thiosemicarbazones/chemistry , Trypanocidal Agents/chemistry , Chromans/chemistry , Electrochemistry , Electron Spin Resonance SpectroscopyABSTRACT
In the search for new therapeutic tools against American Trypanosomiasis palladium complexes with bioactive nitrofuran-containing thiosemicarbazones as ligands were obtained. Sixteen novel palladium (II) complexes with the formulas [PdCl2(HL)] and [Pd(L)2] were synthesized, and the crystal structure of [Pd(5-nitrofuryl-3-acroleine thiosemicarbazone)2] x 3DMSO was solved by X-ray diffraction methods. Most complexes showed higher in vitro growth inhibition activity against Trypanosoma cruzi than the standard drug Nifurtimox. In most cases, the activity of the ligand was maintained or even increased as a result of palladium complexation. In addition, the complexes' mode of antitrypanosomal action was investigated. Although the complexes showed strong DNA binding, all data strongly suggest that the main trypanocidal mechanism of action is the production of oxidative stress as a result of their bioreduction and extensive redox cycling. Moreover, the complexes were found to be irreversible inhibitors of trypanothione reductase.
Subject(s)
DNA/chemistry , Nitrofurans/chemical synthesis , Organometallic Compounds/chemical synthesis , Palladium , Thiosemicarbazones/chemical synthesis , Trypanocidal Agents/chemical synthesis , Animals , Crystallography, X-Ray , Dimethyl Sulfoxide/chemistry , Electrochemistry , Electron Spin Resonance Spectroscopy , Free Radicals/metabolism , Ligands , Magnetic Resonance Spectroscopy , Molecular Structure , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Nitrofurans/chemistry , Nitrofurans/pharmacology , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Oxidation-Reduction , Oxidative Stress , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, Raman , Structure-Activity Relationship , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Trypanosoma cruzi/metabolismABSTRACT
The electrochemistry of 3-alkoxy- and 3-hydroxy-1-[omega-(dialkylamino)alkyl]-5-nitroindazole derivatives were characterized using cyclic voltammetry in DMSO. The nitro reduction process was studied and this was affected by the acid moieties present in these compounds. A nitro anion self-protonation process was observed. This phenomenon was studied by cyclic voltammetry in presence of increasing amount of NaOH. The reactivity of the nitro anion radical of these derivatives with glutathione was also studied by cyclic voltammetry. The oxidizing effect of glutathione is supported by the parallel decrease of the anodic peak current and increase of the cathodic peak in the cyclic voltammograms, corresponding to the wave of the nitro anion radical from uncharged species with the addition of glutathione. Nitro anion radicals obtained by electrolytic reduction of these derivatives were measured and analyzed in DMSO using electron spin resonance spectroscopy.
